Hepatic stellate cell line modulates lipogenic transcription factors

Abstract

Background/aims: Pre-adipocyte differentiation into adipocyte is a terminal differentiation process triggered by a cascade of transcription factors. Conversely, hepatic stellate cells (HSC) can switch between lipid storing and the myofibroblast phenotype in association with liver fibrotic processes. Here, adipogenic/lipogenic-related transcription factors and downstream-regulated genes were evaluated in a murine HSC cell line. GRX-HSC cells are transitional myofibroblasts that differentiate into lipocytes following retinol or indomethacin treatment.

Methods/results: Specific mRNAs were quantified by a real-time polymerase chain reaction after 24 h or 7 days of cell culture with indomethacin or retinol. Proliferator-activated receptorgamma and Pex16 transcripts were increased either by retinol or indomethacin. Retinol induced a minor increase in C/enhancer binding proteinalpha transcripts, while only indomethacin increased adipsin transcripts.

Conclusions: Our results showed that the myofibroblast to lipocyte phenotype switch follows partially different transcriptional pathways, according to the effector. Retinol induces lipid synthesis and storage without affecting characteristic adipocytic genes, while indomethacin treatment restores the lipocytic phenotype with increased adipisin expression.